DESCRIPTION: (Adapted from the Abstract) The long-term objective of this research is to obtain a complete understanding of the progression and physiology of an established colony of genetic hypertensive dogs. These dogs represent a unique model of naturally occurring hypertension that may serve as a useful model of human hypertension. The physiological systems to be studied include cardiac, neural, renal, and endocrine systems that influence extracellular fluid volume and renal regulation of sodium and water. All studies will be conducted in conscious dogs. Dogs for these studies will be produced by a proven breeding strategy within a stable colony located at the University of Pennsylvania. Longitudinal studies of the colony will determine aging effects including cardiac and renal function, and complete necropsy. Specific mechanisms of blood pressure control to be studied include: renal sympathetic activity, renal retention of fluid and/or sodium, effect of calcium channel blockers on cardiac, renal, and endocrine mechanisms, influence of renal effects of dopamine agonists and antagonists, cross transplantation of kidneys to determine whether hypertension follows the kidney, and influences of cardiac dysfunction on high blood pressure during aging. A group of cardiac and renal function tests will be serially performed in the breeding colony. Special physiologic tests to be used include: chronic instrumentation of dogs to determine cardiac function, chronic renal function curves, renal denervation, continuous monitoring of hemodynamic variables in special metabolic pens, measurement and/or servo-control of total body weight, servo-control of arterial pressure, and recording of renal sympathetic nerve activity. These studies will be performed on related normotensive dogs, borderline hypertensives, and salt-sensitive and salt-resistant hypertensive dogs. These studies should lead to a more complete physiologic and pathologic characterization of the model. As the mechanisms of hypertension are revealed, a major objective is to collaborate with a commercial breeder to make these dogs generally available to the scientific community.